Dataset Information

Mouse Liver Lysine β-hydroxybutyrylome

ABSTRACT: Characterization of the lysine β-hydroxybutyrylome, proteome-wide, will start to define its cellular targets and enable investigation of its impact under ketogenesis. Here, we show the induction of global protein Kbhb in the liver. We identified 891 sites of Kbhb within 267 proteins belonging to macronutrient, detoxification and 1-carbon metabolic pathways, among others, in starved liver.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: He Huang

LAB HEAD: Yingming Zhao

PROVIDER: PXD016654 | Pride | 2021-09-08

REPOSITORIES: Pride

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Publications

Ketogenesis impact on liver metabolism revealed by proteomics of lysine β-hydroxybutyrylation.

Koronowski Kevin B KB Greco Carolina M CM Huang He H Kim Jin-Kwang JK Fribourgh Jennifer L JL Crosby Priya P Mathur Lavina L Ren Xuelian X Partch Carrie L CL Jang Cholsoon C Qiao Feng F Zhao Yingming Y Sassone-Corsi Paolo P

Cell reports 20210801 5

Ketone bodies are bioactive metabolites that function as energy substrates, signaling molecules, and regulators of histone modifications. β-hydroxybutyrate (β-OHB) is utilized in lysine β-hydroxybutyrylation (Kbhb) of histones, and associates with starvation-responsive genes, effectively coupling ketogenic metabolism with gene expression. The emerging diversity of the lysine acylation landscape prompted us to investigate the full proteomic impact of Kbhb. Global protein Kbhb is induced in a tiss ...[more]

PMID: 34348140

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Project description:Gene expression studies in peripheral blood mononuclear cells (PBMC) can provide knowledge that would be difficult to obtain using other types of biological samples, as these cells can reflect overall response of the body to a specific stimulus, such as diet. Here, we aimed to study the impact of sustained intake of isocaloric diets with an unbalanced macronutrient proportion (rich in fat or protein) on PBMC gene expression in rats using transcriptomics, to better understand the effects of these diets on metabolism and health. Macronutrient diet composition (especially increased protein content) affected PBMC gene expression. An important effect was observed in immune response-related genes. High protein (HP) diet produced an activation of genes mainly related to antigen recognition/presentation, whereas the high fat (HF) diet was more related to a decreased expression of these genes. Key energy homeostasis genes (mainly involved in lipid metabolism) were also affected, reflecting a nutritional adaptive response to the diets. Decreased Dhrs3 and increased Pref-1/Dlk1 expression observed in HP-fed animals reflects a lower lipogenic capacity. In addition, HF diet affected the expression of genes related to insulin resistance/signaling (Msra/Slc9a6, Asb6), hypoxia (Akap12), cardiovascular problems (Ethe1, Lr11), cognitive impairment (Tmcc2) and tumorigenesis (Ddx17, Phb, Rnasen/Drosha, and Tsc2). HP diet also impaired the expression of genes related to glucose metabolism and insulinemia (Glut-4/Slc2a4, Sfxn5, Slc16a1), but positively affected genes involved in liver function (Clec4f and St6galnac3) and cardiovascular protection (Sort1). In conclusion, gene expression analysis in PBMC can provide information that could be useful to detect metabolic deviations and health consequences of diets with an unbalanced macronutrient composition. 2 months-old male Wistar rats received a low fat control diet, or a high fat (HF) diet, or a high protein (HP) diet for 4 months, respectively. At the end of the intervention, prior to the sacrifice of the animals, peripheral blood samples (1.5-2.5 mL) were collected from the safena vein, using heparin in NaCl (0.9%) as anticoagulant. Immediately after blood collection, peripheral blood mononuclear cells (PBMC) were isolated by Ficoll gradient separation. Total RNA was isolated from PBMC, quantified and qualified, and subsequently used for global gene expression profiling using Agilent 4x44K microarrays.

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